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Safety and Efficacy Study Evaluating TRx0237 in Subjects With Behavioral Variant Frontotemporal Dementia (bvFTD)

Sponsor
TauRx Therapeutics Ltd (Industry)
Overall Status
Completed
CT.gov ID
NCT01626378
Collaborator
(none)
220
Enrollment
67
Locations
2
Arms
33.1
Duration (Months)
3.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to demonstrate the safety and efficacy of TRx0237 in the treatment of patients with behavioral variant frontotemporal dementia (bvFTD).

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
220 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Double-Blind, Placebo-Controlled, Randomized, Parallel Group, 12-Month Safety and Efficacy Trial of TRx0237 in Subjects With Behavioral Variant Frontotemporal Dementia (bvFTD)
Study Start Date :
May 1, 2013
Actual Primary Completion Date :
Feb 1, 2016
Actual Study Completion Date :
Feb 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: TRx0237 200 mg/day group

Drug: TRx0237
TRx0237 100 mg tablet will be administered twice daily.
Placebo Comparator: Placebo

Drug: Placebo
Placebo tablets will be administered twice daily. The placebo tablets include 4 mg of TRx0237 as a urinary and fecal colorant to maintain blinding; hence, the placebo group will receive a total of 8 mg/day of TRx0237.

Outcome Measures

Primary Outcome Measures

  1. Change from Baseline on Addenbrooke's Cognitive Examination - Revised (ACE-R) [52 weeks]

  2. Change from Baseline on Functional Activities Questionnaire (FAQ) [52 weeks]

  3. Change from Baseline on whole brain volume (assessed by brain MRI) [52 weeks]

Secondary Outcome Measures

  1. Change from Baseline on Unified Parkinson's Disease Rating Scale (UPDRS Parts II and III) [52 weeks]

  2. Change from Baseline on Frontotemporal Dementia Rating Scale (FRS) [52 weeks]

  3. Change from Baseline on Modified Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (modified ADCS-CGIC) [52 weeks]

  4. Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes [52 weeks]

    Safety parameters included adverse events, vital signs, methemoglobin and oxygen saturation, physical and neurological examinations, laboratory tests (hematology, serum chemistry, and urinalysis), electrocardiograms, assessment of serotonin syndrome, brain magnetic resonance imaging (MRI) and potential for suicidal behavior and thoughts

Other Outcome Measures

  1. Early effect on modified ADCS-CGIC (change from Baseline) [8 weeks]

  2. Change from Baseline on the rate of atrophy in frontal and temporal lobes as well as ventricular volume (assessed by brain MRI) [52 weeks]

  3. Change from Baseline on Mini-Mental Status Examination (MMSE) [52 weeks]

  4. Change from Baseline on Addenbrooke's Cognitive Examination-III (ACE-III) [52 weeks]

  5. Determine the effect of TRx0237 in subjects with known genetic mutations associated with bvFTD [52 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:
N/A to 79 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Diagnosis of probable bvFTD

  • Centrally rated frontotemporal atrophy score of 2 or greater on brain MRI

  • MMSE ≥20

  • Age <80 years

  • Modified Hachinski ischemic score of ≤ 4

  • Females, if of child-bearing potential, must practice true abstinence or be competent to use adequate contraception and agree to maintain this throughout the study

  • Subject, and/or, in the case of reduced decision-making capacity, legally acceptable representative(s) consistent with national law is/are able to read, understand, and provide written informed consent

  • Has one (or more) identified adult caregiver who is willing to provide written informed consent for his/her own participation; is able to read, understand, and speak the designated language at the study site; either lives with the subject or sees the subject for ≥2 hours/day ≥3 days/week; agrees to accompany the subject to each study visit; and is able to verify daily compliance with study drug

  • If currently taking an acetylcholinesterase inhibitor and/or memantine, the subject must have been taking such medication(s) for ≥3 months. The dosage regimen must have remained stable for ≥6 weeks and it must be planned to remain stable throughout participation in the study.

  • Able to comply with the study procedures

Exclusion Criteria:

  • Significant central nervous system (CNS) disorder other than bvFTD

  • Significant intracranial pathology seen on brain MRI scan

  • Biomarker evidence of underlying Alzheimer's disease pathology

  • Expressive language deficits

  • Meets research criteria for Amyotrophic Lateral Sclerosis or motor neuron disease

  • Meets diagnostic criteria for probable bvFTD but has a proven mutation producing non-tau, non-TDP-43 pathology

  • Clinical evidence or history of stroke, transient ischemic attack, significant head injury or other unexplained or recurrent loss of consciousness ≥15 minutes

  • Epilepsy

  • Rapid eye movement sleep behavior disorder

  • Major depressive disorder, schizophrenia, or other psychotic disorders, bipolar disorder, substance (including alcohol) related disorders

  • Metal implants in the head (except dental), pacemaker, cochlear implants, or any other non-removable items that are contraindications to MRI

  • Resides in hospital or moderate to high dependency continuous care facility

  • History of swallowing difficulties

  • Pregnant or breastfeeding

  • Glucose-6-phosphate dehydrogenase deficiency

  • History of significant hematological abnormality or current acute or chronic clinically significant abnormality

  • Abnormal serum chemistry laboratory value at Screening deemed to be clinically relevant by the investigator

  • Clinically significant cardiovascular disease or abnormal assessments

  • Preexisting or current signs or symptoms of respiratory failure

  • Concurrent acute or chronic clinically significant immunologic, hepatic, or endocrine disease (not adequately treated) and/or other unstable or major disease other than bvFTD

  • Diagnosis of cancer within the past 2 years prior to Baseline (other than basal cell or squamous cell skin cancer or Stage 1 prostate cancer) unless treatment has resulted in complete freedom from disease for at least 2 years

  • Prior intolerance or hypersensitivity to methylthioninium-containing drug, similar organic dyes, or any of the excipients

  • Treatment currently or within 90 days before Baseline with any of the following medications (unless otherwise noted):

  • Tacrine

  • Amphetamine or dexamphetamine

  • Clozapine, olanzapine (and there is no intent to initiate therapy during the course of the study)

  • Carbamazepine, primidone

  • Drugs for which there is a warning or precaution in the labeling about methemoglobinemia at approved doses

  • Current or prior participation in a clinical trial as follows:

  • Clinical trial of a product for cognition within 3 months of Screening (unless confirmed to have been randomized to placebo)

  • A clinical trial of a drug, biologic, device, or medical food in which the last dose/administration was received within 28 days prior to Baseline

Contacts and Locations

Locations

Site City State Country Postal Code
1 David Geffen School of Medicine at UCLA, UCLA Neurological Services Los Angeles California United States 90095
2 The Shankle Clinic Newport Beach California United States 92663
3 Memory and Aging Centre San Francisco California United States 94158
4 Meridien Research Brooksville Florida United States 34601
5 Mayo Clinic Jacksonville Florida United States 32224
6 Compass Research, LLC Orlando Florida United States 32806
7 University of South Florida Tampa Florida United States 33613
8 Department of Neurology, Emory University Atlanta Georgia United States 30329
9 Alexian Brothers Neurosciences Institute Clinical Research Elk Grove Village Illinois United States 60007
10 Indiana University Department of Neurology Indianapolis Indiana United States 46202
11 Johns Hopkins University Baltimore Maryland United States 21224
12 Neurological Clinical Research Institute (NCRI) Massachusetts General Hospital Boston Massachusetts United States 02114
13 Mayo Clinic, Department of Neurology Rochester Minnesota United States 55905
14 Memory Enhancement Center of America, Inc. Eatontown New Jersey United States 07724
15 Neurological Associates of Albany, P. C. Albany New York United States 12208
16 Integrative Clinical Trials LLC Brooklyn New York United States 11229
17 UNC Department of Neurology, Physicians Office Building Chapel Hill North Carolina United States 27599
18 University Hospitals Case Medical Center, Neurology Clinical Trials Unit Cleveland Ohio United States 44106
19 Rivers Wellness and Research Institute Oklahoma City Oklahoma United States 73112
20 The Clinical Trial Center, LLC Jenkintown Pennsylvania United States 19046
21 Hospital of the University of Pennsylvania, Department of Neurology Philadelphia Pennsylvania United States 19104
22 PRA Health Sciences, Phase 2/3 Outpatient and CNS Clinic Salt Lake City Utah United States 84106
23 The Memory Clinic Bennington Vermont United States 05201
24 University of Virginia Charlottesville Virginia United States 22903
25 Neuroscience Research Australia Randwick New South Wales Australia 2031
26 Box Hill Hospital Box Hill Victoria Australia 3128
27 Neurodegenerative Disorders Research Pty Ltd West Perth Western Australia Australia 6005
28 Heritage Medical Research Clinic-University of Calgary Calgary Alberta Canada T2N 4Z6
29 University of British Columbia Hospital, Clinic for Alzheimer Disease and Related Disorders Vancouver British Columbia Canada V6T 2B5
30 Vancouver Island Health Authority Victoria British Columbia Canada V8R 1J8
31 True North Clinical Research Halifax Nova Scotia Canada B3S 1M7
32 Geriatric Clinical Trials Group, Parkwood Institute London Ontario Canada N6C 0A7
33 Toronto Memory Program Toronto Ontario Canada M3B 2S7
34 University Health Network, Toronto Western Hospital, Memory Clinic Toronto Ontario Canada M5T 2S8
35 McGill Centre for Studies in Aging, Alzheimer Disease Research Unit Verdun Quebec Canada H4H 1R3
36 University Hospital Centre Zagreb Zagreb Croatia 10000
37 University Psychiatric Hospital Vrapče Zagreb Croatia 10090
38 Charité-Universitätsmedizin Berlin Klinik für Psychiatrie und Psychotherapie Berlin Germany 10117
39 Memory Clinic, ECRC Berlin Germany 13125
40 Universitätsklinikum Hamburg-Eppendorf Klinik für Psychiatrie und Psychotherapie Hamburg Germany 20246
41 Klinik und Poliklinik für Psychiatrie und Psychotherapie der Technischen Universität München München Germany 81675
42 Universitäts - und Rehabilitationskliniken Ulm, Neurologie Ulm Germany 89081
43 Unità di Neuroimmagine e Epidemiologia Alzheimer Brescia Italy 25125
44 Fondazione Universita' Gabriele D'Annunzio di Chieti Chieti Scalo Italy 66100
45 Fondazione IRCCS Istituto Neurologico "Carlo Besta" Milano Italy 20133
46 Neurology I, Department of Neuroscience, University of Torino Torino Italy 10126
47 Alzheimer Research Center Amsterdam Amsterdam Netherlands 1081
48 Jeroen Bosch Ziekenhuis, afdeling geriatrie Den Bosch Netherlands 5223
49 Erasmus University Medical Center Rotterdam Netherlands 3015
50 NZOZ Neuro-Kard Ilkowski i Partnerzy Spółka Partnerska Poznań Poland 61-853
51 Euromedis Sp. z o.o. Szczecin Poland 70-111
52 Psychomedical Consult Bucharest Romania 024072
53 National Neuroscience Institute Department of Neurology Singapore Singapore 308433
54 Fundació ACE. Institut Català de Neurociències Aplicades Barcelona Spain 08028
55 Ceuta University Hospital; Neurology Ceuta Spain 51003
56 Hospital Viamed Montecanal, Neurology Department Zaragoza Spain 50012
57 NHS Grampian, OAP Directorate Aberdeen United Kingdom AB25 2ZH
58 The Barberry Out-Patients Department Birmingham United Kingdom B15 2FG
59 2gether NHS foundation trust Cheltenham United Kingdom GL53 9DZ
60 Kingsway Hospital Derby United Kingdom DE22 3LZ
61 St Margaret's Hospital Mental Health Unit Epping United Kingdom CM16 6TN
62 Cognition Health Ltd. London United Kingdom W1G 9JF
63 Imperial College Healthcare NHS Trust - Charing Cross Hospital London United Kingdom W6 8RF
64 Dementia Research Center at Queens Square London United Kingdom WC1N 3BG
65 Nuffield Department of Clinical Neurosciences Oxford United Kingdom OX3 9DU
66 Redwoods Centre Shrewsbury United Kingdom SY3 5DS
67 Wessex Neurological Centre, Southampton General Hospital Southampton United Kingdom SO16 6YD

Sponsors and Collaborators

  • TauRx Therapeutics Ltd

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
TauRx Therapeutics Ltd
ClinicalTrials.gov Identifier:
NCT01626378
Other Study ID Numbers:
  • TRx-237-007
First Posted:
Jun 22, 2012
Last Update Posted:
Mar 14, 2018
Last Verified:
Mar 1, 2018
Keywords provided by TauRx Therapeutics Ltd
Behavioral Variant Frontotemporal Dementia
bvFTD
Frontotemporal Dementia
Additional relevant MeSH terms:
Dementia
Frontotemporal Dementia
Aphasia, Primary Progressive
Pick Disease of the Brain

Study Results

No Results Posted as of Mar 14, 2018